Corrigendum to: Subgroup analysis of Japanese patients in a Phase 3 study of atezolizumab in advanced triple-negative breast cancer (IMpassion130)

Abstract Background In the randomised Phase 3 IMpassion130 trial, atezolizumab combined with nab-paclitaxel (atezo + nab-P) in 902 patients with triple-negative breast cancer (TNBC) showed prolonged progression-free survival (PFS) in both the intention-to-treat (ITT) population and programmed death-ligand 1 (PD-L1)–positive subgroup compared with placebo plus nab-P (plac + nab-P). This study assessed the efficacy and safety of atezo + nab-P in the IMpassion130 Japanese subpopulation. Methods Eligible patients had unresectable locally advanced or metastatic TNBC previously untreated with chemotherapy for metastatic disease. Patients were randomised 1:1 to receive either atezo + nab-P or plac + nab-P. Co-primary endpoints were investigator-assessed PFS and overall survival (ITT population and PD-L1–positive subgroup). These were also assessed in the Japanese subpopulation. Results There were 65 Japanese patients (34 atezo + nab-P; 31 plac + nab-P). The PD-L1–positive subgroup included 25 patients (12 atezo + nab-P; 13 plac + nab-P). Median PFS was 7.4 months (atezo + nab-P) versus 4.6 months (plac + nab-P; hazard ratio [HR], 0.47; 95% CI, 0.25–0.90). In the PD-L1–positive subgroup, median PFS was 10.8 months (atezo + nab-P) versus 3.8 months (plac + nab-P; HR, 0.04; 95% CI, <0.01–0.35). Safety results in the Japanese subgroup were consistent with those in the overall population. The Japanese subgroup had a lower incidence of adverse events leading to treatment withdrawal than the overall population. More patients in the atezo + nab-P arm had neutrophil count decreases and stomatitis than patients in the plac + nab-P arm. Conclusions Atezo + nab-P efficacy in Japanese patients was consistent with the overall IMpassion130 population. No new safety signals were observed, and tolerability was consistent with that of the overall population.

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Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial

The Lancet Oncology ◽

10.1016/s1470-2045(20)30754-3 ◽

2021 ◽

Vol 22 (4) ◽

pp. 499-511 ◽

Cited By ~ 1

Author(s):

Eric P Winer ◽

Oleg Lipatov ◽

Seock-Ah Im ◽

Anthony Goncalves ◽

Eva Muñoz-Couselo ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Open Label ◽

Phase 3 ◽

Open Label Phase

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Actionable Gene Alterations in an Asian Population With Triple-Negative Breast Cancer

JCO Precision Oncology ◽

10.1200/po.17.00211 ◽

2018 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Masayuki Nagahashi ◽

YiWei Ling ◽

Tetsu Hayashida ◽

Yuko Kitagawa ◽

Manabu Futamura ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Ethnic Diversity ◽

Triple Negative ◽

Asian Population ◽

Japanese Patients ◽

The United States ◽

The Cancer Genome Atlas ◽

Cancer Genes ◽

Asian Patients

Purpose It has been suggested that the biologic characteristics of breast cancer may differ among different geographic or ethnic populations. Indeed, triple-negative breast cancer (TNBC), the most lethal breast cancer subgroup, has been reported to occur at a higher incidence in Japan than in the United States. However, most genomic studies of these tumors are from Western countries, and the genomic landscape of TNBC in an Asian population has not been thoroughly investigated. Here, we sought to elucidate the geographic and ethnic diversity of breast cancer by examining actionable driver alterations in TNBC tumors from Japanese patients and comparing them with The Cancer Genome Atlas (TCGA) database, which gathers data primarily from non-Asian patients. Materials and Methods We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes, among Japanese patients with TNBC (n = 53) and compared the results with independent data obtained from TCGA (n = 123). Results Driver alterations were identified in 51 (96%) of 53 Japanese patients. Although the overall alteration spectrum among Japanese patients was similar to that of TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutational burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35 of 53) of Japanese patients, as well as 66.7% (82 of 123) of TCGA cohort, had alterations in at least one actionable gene targetable by US Food and Drug Administration–approved drug. Conclusion Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.

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Abstract OT3-02-10: Nordic trip, a randomized phase 3 study in early triple negative breast cancer

10.1158/1538-7445.sabcs15-ot3-02-10 ◽

2016 ◽

Cited By ~ 1

Author(s):

N Loman ◽

B Linderholm ◽

H Joensuu ◽

B Ejlertsen ◽

OT Johannsson ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Phase 3

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ALEXANDRA/IMpassion030: A phase III study of standard adjuvant chemotherapy with or without atezolizumab in early-stage triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps598 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS598-TPS598

Author(s):

Heather L. McArthur ◽

Michail Ignatiadis ◽

Sebastian Guillaume ◽

Andrew Bailey ◽

Jorge Luis Martinez ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Early Stage ◽

Disease Free Survival ◽

Phase Iii ◽

Lymph Node Status ◽

Phase 3 ◽

Metastatic Setting

TPS598 Background: Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer and promising clinical activity has been reported with the anti–PD-L1 antibody, atezolizumab, in Phase 1/1b metastatic TNBC trials. Furthermore, the randomized phase 3 IMpassion130 study demonstrated enhanced anti-tumor activity when atezolizumab was co-administered with chemotherapy in the first line metastatic setting, with benefit mainly observed in PD-L1+ cohort. ALEXANDRA/IMpassion030 will evaluate the efficacy and safety of atezolizumab in combination with standard anthracycline/taxane adjuvant chemotherapy in early TNBC patients. Methods: ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard chemotherapy versus chemotherapy alone in early TNBC. In total, 2300 patients with operable stage II or III TNBC, confirmed by central pathology review, will be randomized. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant treatment will consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary end-point is invasive disease-free survival (iDFS) and secondary end-points include iDFS by PD-L1 and lymph node status, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first patient was enrolled on August 2nd 2018, and approximately 430 sites are expected to be opened globally in 30 countries. Clinical trial information: NCT03498716.

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